The expression and control of bioregulatory macromolecules in fetal development and the effects of their interactions on cellular proliferation, differentiation and immunocompetence compared to related factors of tumor cell origin are under investigation. The interferon-like activity found in placental tissues of the mouse (MuIFN-P1) was examined in depth because of the well-established antiproliferative properties which the interferons exhibit in several neoplastic diseases and tissue culture systems, and their known immunomodulatory effects. MuIFN-P1 was found, through the use of several antisera, to be serologically distinct from the classical families of mouse interferons. The antiviral state induced by MuIFN-P1 was more stable than that induced by the classical interferons in kinetic studies examining the persistence of cytoprotective and yield inhibitory functions against both positive and negative strains RNA viruses (MM and vesicular stomatitis viruses). MuIFN-Pl was nonetheless found to possess the characteristics of a bona fide interferon in that it is a soluble protein requiring a time-dependent cellular transcriptional event, it is highly specific for mouse cells, it primes for the increased production of type-1 interferon at optimal concentrations similar to the optima for the classical interferons, and it induces the production of 2-5 A synthetase specifically in mouse cells and in a time-dependent manner. Further, MuIFN-P1 treatment of target cells suppresses their vulnerability to natural killer cells. Placental interferon is not unique to the mouse, but occurs in other rodents which have been examined (rat and hamster), as well as in man and the patas monkey.